Lead poisoning causes a hypochromic microcytic anemia with basophilic stippling of erythrocytes. The primary biochemical mechanism of lead-induced anemia involves inhibition of which two enzymes in heme synthesis?

• A ALA synthase and uroporphyrinogen cosynthase
• B PBG deaminase and coproporphyrinogen oxidase
• C ALA dehydratase (ALAD) and ferrochelatase ✓
• D Uroporphyrinogen decarboxylase and protoporphyrinogen oxidase

Explanation

Lead has high affinity for sulfhydryl groups and inhibits two zinc-dependent enzymes: ALA dehydratase (condensation of two ALA to PBG, the second step) and ferrochelatase (insertion of Fe2+ into protoporphyrin IX, the final step). Ferrochelatase inhibition causes zinc protoporphyrin (ZPP) accumulation in erythrocytes, a sensitive screening marker. Lead also inhibits the ribosomal RNase that normally degrades rRNA, causing ribosomal aggregates that appear as basophilic stippling on Wright's-stained peripheral smear.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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